The ALT pathway generates telomere fusions that can be detected in the blood of cancer patients.

Telomere fusions (TFs) can trigger the accumulation of oncogenic alterations leading to malignant transformation and drug resistance. Despite their relevance in tumour evolution, our understanding of the patterns and consequences of TFs in human cancers remains limited. Here, we characterize the rat...

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Detalhes bibliográficos
Autores: Muyas, Francesc, Rodriguez, Manuel José Gómez, Cascão, Rita, Afonso, Angela, Sauer, Carolin M, Faria, Claudia C, Cortés-Ciriano, Isidro, Flores, Ignacio
Formato: artículo
Fecha de publicación:2024
País:España
Recursos:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/19366
Acesso em linha:http://hdl.handle.net/20.500.12105/19366
Access Level:acceso abierto
Palavra-chave:Telomerase
Neoplasms
Humans
Telomere Homeostasis
Telomere
Genomics
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spelling The ALT pathway generates telomere fusions that can be detected in the blood of cancer patients.Muyas, FrancescRodriguez, Manuel José GómezCascão, RitaAfonso, AngelaSauer, Carolin MFaria, Claudia CCortés-Ciriano, IsidroFlores, IgnacioTelomeraseNeoplasmsHumansTelomere HomeostasisTelomereGenomicsTelomere fusions (TFs) can trigger the accumulation of oncogenic alterations leading to malignant transformation and drug resistance. Despite their relevance in tumour evolution, our understanding of the patterns and consequences of TFs in human cancers remains limited. Here, we characterize the rates and spectrum of somatic TFs across >30 cancer types using whole-genome sequencing data. TFs are pervasive in human tumours with rates varying markedly across and within cancer types. In addition to end-to-end fusions, we find patterns of TFs that we mechanistically link to the activity of the alternative lengthening of telomeres (ALT) pathway. We show that TFs can be detected in the blood of cancer patients, which enables cancer detection with high specificity and sensitivity even for early-stage tumours and cancers of high unmet clinical need. Overall, we report a genomic footprint that enables characterization of the telomere maintenance mechanism of tumours and liquid biopsy analysis.Nature Publishing GroupWellcome TrustMinisterio de Ciencia e Innovación (España)Comunidad de Madrid (España)Ministerio de Ciencia, Innovación y Universidades (España)Ministerio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España)20242024-05-1020242024-01-0220242024-01-02journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/20.500.12105/19366reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/193662026-06-12T12:43:37Z
dc.title.none.fl_str_mv The ALT pathway generates telomere fusions that can be detected in the blood of cancer patients.
title The ALT pathway generates telomere fusions that can be detected in the blood of cancer patients.
spellingShingle The ALT pathway generates telomere fusions that can be detected in the blood of cancer patients.
Muyas, Francesc
Telomerase
Neoplasms
Humans
Telomere Homeostasis
Telomere
Genomics
title_short The ALT pathway generates telomere fusions that can be detected in the blood of cancer patients.
title_full The ALT pathway generates telomere fusions that can be detected in the blood of cancer patients.
title_fullStr The ALT pathway generates telomere fusions that can be detected in the blood of cancer patients.
title_full_unstemmed The ALT pathway generates telomere fusions that can be detected in the blood of cancer patients.
title_sort The ALT pathway generates telomere fusions that can be detected in the blood of cancer patients.
dc.creator.none.fl_str_mv Muyas, Francesc
Rodriguez, Manuel José Gómez
Cascão, Rita
Afonso, Angela
Sauer, Carolin M
Faria, Claudia C
Cortés-Ciriano, Isidro
Flores, Ignacio
author Muyas, Francesc
author_facet Muyas, Francesc
Rodriguez, Manuel José Gómez
Cascão, Rita
Afonso, Angela
Sauer, Carolin M
Faria, Claudia C
Cortés-Ciriano, Isidro
Flores, Ignacio
author_role author
author2 Rodriguez, Manuel José Gómez
Cascão, Rita
Afonso, Angela
Sauer, Carolin M
Faria, Claudia C
Cortés-Ciriano, Isidro
Flores, Ignacio
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Wellcome Trust
Ministerio de Ciencia e Innovación (España)
Comunidad de Madrid (España)
Ministerio de Ciencia, Innovación y Universidades (España)
Ministerio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España)
dc.subject.none.fl_str_mv Telomerase
Neoplasms
Humans
Telomere Homeostasis
Telomere
Genomics
topic Telomerase
Neoplasms
Humans
Telomere Homeostasis
Telomere
Genomics
description Telomere fusions (TFs) can trigger the accumulation of oncogenic alterations leading to malignant transformation and drug resistance. Despite their relevance in tumour evolution, our understanding of the patterns and consequences of TFs in human cancers remains limited. Here, we characterize the rates and spectrum of somatic TFs across >30 cancer types using whole-genome sequencing data. TFs are pervasive in human tumours with rates varying markedly across and within cancer types. In addition to end-to-end fusions, we find patterns of TFs that we mechanistically link to the activity of the alternative lengthening of telomeres (ALT) pathway. We show that TFs can be detected in the blood of cancer patients, which enables cancer detection with high specificity and sensitivity even for early-stage tumours and cancers of high unmet clinical need. Overall, we report a genomic footprint that enables characterization of the telomere maintenance mechanism of tumours and liquid biopsy analysis.
publishDate 2024
dc.date.none.fl_str_mv 2024
2024-05-10
2024
2024-01-02
2024
2024-01-02
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12105/19366
url http://hdl.handle.net/20.500.12105/19366
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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